When 2-D gel electrophoresis is used to separate a mixture of proteins, a high degree of separation can be achieved. The generation of charged derivatives offers substantial advantages when the analytes are subsequently prepared for MALDI analysis. However, the introduction of solutions to introduce reagents results in diffusion of analytes, degrading the separation. We are pursuing the gas phase introduction of reagents, for the derivatization of peptides and proteins on membranes. Membranes containing peptides can either be exposed to gas phase reagents, or the gaseous reagents can be perfused through the membrane, by using a vacuum on one side and a source of reagent on the other. When a peptide on a membrane is exposed to chloroacetyl chloride (g), this reacts with the N-terminus, eliminating HCI. The remaining CI can be displaced by a variety of bases such as trimethyyl amine (g) to make the N-terminal charged derivative. MALDI matrix can then be introduced for direct desorption of the derivatized analyte(s) from the membrane surface. Conditions are being optimized for such reactions, and bases are being investigated which will form charged-derivatives that yield structural information in the PSD experiment.